Library of compounds comprising pyrrolobenzodiazepine moieties
View Patent ↗A compound of formula (IV): O is a solid support; L is a linking group or a single bond; X′ is selected from CO, NH, S, or O; A is O, S, NH, or a single bond; R 2 and R 3 are independently selected from: H, R, OH, OR, ═O, ═CH—R, ═CH 2 , CH 2 —CO 2 R, CH 2 —CO 2 H, CH 2 —SO 2 R, O—SO 2 R, CO 2 R, COR, CN and there is optionally a double bond between C1 and C2 or C2 and C3; R 6 , R 7 , and R 9 are independently selected from H, R, OH, OR, halo, nitro, amino, Me 3 Sn; R 11 is either H or R; Q is S, O or NH; R 10 is a nitrogen protecting group; and Y is a divalent group such that HY═R, and other related compounds and collections of compounds.
1. A collection of compounds all of which are represented by formula II:
wherein:
A is O, S, NH, or a single bond;
R 2 and R 3 are independently selected from: H, R, OH, OR, ═O, ═CH—R, ═CH 2 , CH 2 —CO 2 R, CH 2 —CO 2 H, CH 2 —SO 2 R, O—SO 2 R, CO 2 R, COR, CN and there is optionally a double bond between C2 and C3;
R 6 , R 7 , and R 9 are independently selected from H, R, OH, OR, halo, nitro, amino, Me 3 Sn; where R is an alkyl group having 1 to 10 carbon atoms, or an aralkyl group of up to 12 carbon atoms whereof the alkyl group optionally contains one or more carbon-carbon double or triple bonds, which may form part of a conjugated system, or an aryl group of up to 12 carbon atoms;
and is optionally substituted by one or more halo, hydroxy, amino, or nitro groups, and optionally contains one or more hetero atoms which may form part of, or be, a functional group;
Y is a divalent group such that HY═R;
X′ is CO, NH, S or O;
T is an amino acid residue combinatorial unit, where each T may be different if n is greater than 1; and
n is a positive integer from 1 to 16.
2. A collection of compounds according to claim 1 wherein R and HY are independently selected from lower alkyl group having 1 to 10 carbon atoms, or an aralkyl group of up to 12 carbon atoms, or an aryl group of up to 12 carbon atoms, optionally substituted by one or more halo, hydroxy, amino, or nitro groups.
3. A collection of compounds according to claim 1 , wherein R and HY are independently selected from lower alkyl groups having 1 to 10 carbon atoms optionally substituted by one or more halo, hydroxy, amino, or nitro groups.
4. A collection of compounds according to claim 1 , wherein R or HY are independently selected from unsubstituted straight or branched chain alkyl groups, having 1 to 10 carbon atoms.
5. A collection of compounds according to claim 1 wherein R 7 is an electron donating group.
6. A collection of compounds according to claim 1 wherein R 6 and R 9 are H.
7. A collection of compounds according to claim 1 , wherein R 2 and R 3 of are H.
8. A collection of compounds according to claim 7 , wherein R 7 is an alkoxy group.
9. A collection of compounds according to claim 1 wherein there is no double bond between C2 and C3.
10. A collection of compounds according to claim 1 , wherein —Y-A- is an alkoxy chain.
11. A collection of compounds according to claim 1 , wherein X′ is either CO or NH.
12. A collection of compounds all of which are represented by formula III:
wherein:
A is O, S, NH, or a single bond;
R 2 and R 3 are independently selected from: H, R, OH, OR, ═O, ═CH—R, ═CH 2 , CH 2 —CO 2 R, CH 2 —CO 2 H, CH 2 —SO 2 R, O—SO 2 R, CO 2 R, COR, CN and there is optionally a double bond between C2 and C3;
R 6 , R 7 , and R 9 are independently selected from H, R, OH, OR, halo, nitro, amino, Me 3 Sn; where R is an alkyl group having 1 to 10 carbon atoms, or an aralkyl group of up to 12 carbon atoms whereof the alkyl group optionally contains one or more carbon-carbon double or triple bonds, which may form part of a conjugated system, or an aryl group of up to 12 carbon atoms; and is optionally substituted by one or more halo, hydroxy, amino, or nitro groups, and optionally contains one or more hetero atoms which may form part of, or be, a functional group;
Y is a divalent group such that HY═R;
X′ is CO, NH, S or O;
T is an amino acid residue combinatorial unit, where each T may be different if n is greater than 1;
n is a positive integer from 1 to 16;
L is a linking group, or a single bond; and
is a solid support.
13. A collection of compounds all of which are represented by formula IV:
wherein:
A is O, S, NH, or a single bond;
R 2 and R 3 are independently selected from: H, R, OH, OR, ═O, ═CH—R, ═CH 2 , CH 2 —CO 2 R, CH 2 —CO 2 H, CH 2 —SO 2 R, O—SO 2 R, CO 2 R, COR, CN and there is optionally a double bond between C2 and C3;
R 6 , R 7 , and R 9 are independently selected from H, R, OH, OR, halo, nitro, amino, Me 3 Sn; where R is an alkyl group having 1 to 10 carbon atoms, or an aralkyl group of up to 12 carbon atoms whereof the alkyl group optionally contains one or more carbon-carbon double or triple bonds, which may form part of a conjugated system, or an aryl group of up to 12 carbon atoms; and is optionally substituted by one or more halo, hydroxy, amino, or nitro groups, and optionally contains one or more hetero atoms which may form part of, or be, a functional group;
Y is a divalent group such that HY═R;
X′ is CO, NH, S or O;
T is an amino acid residue combinatorial unit, where each T may be different if n is greater than 1;
L is a linking group, or a single bond;
is a solid support;
n is a positive integer from 1 to 16;
R 11 is either H or R;
Q is S, O or NH; and
R 10 is a nitrogen protecting group.
14. A collection of compounds according to claim 13 , wherein R 10 has a carbamate functionality where it binds to the nitrogen atom at the 10 position of a PBD ring structure.
15. A collection of compounds according to claim 13 , wherein Q is O, and/or R 11 is H.